Current analysis apparatuses, as are routinely used in analytics, forensics, microbiology and clinical diagnostics, are able to carry out a multiplicity of detection reactions and analyses with a multiplicity of samples. In order to be able to carry out a multiplicity of tests in an automated manner, various automatically operating devices for the spatial transfer of measurement cells, reaction containers and reagent liquid containers are required, e.g., transfer arms with gripper functions, transport belts or rotatable transport wheels, and also devices for transferring liquids, e.g., pipetting devices. The apparatuses comprise a central control unit which, by means of appropriate software, is able, in a largely autonomous manner, to plan and work through the work steps for the desired analyses.
Many of the analysis methods used in such analysis apparatuses operating in an automated manner are based on optical methods. Measurement systems based on photometric (e.g. turbidimetric, nephelometric, fluorometric or luminometric) or radiometric measurement principles are particularly widespread. These methods permit the qualitative and quantitative detection of analytes in liquid samples without having to provide additional separation steps. The determination of clinically relevant parameters, for example the concentration or the activity of an analyte, is often carried out by an aliquot of a bodily fluid of a patient being mixed simultaneously or in succession with one or more test reagents in a reaction vessel, as a result of which a biochemical reaction is set in motion, which brings about a measurable change in an optical property of the test preparation.
The measurement result is in turn forwarded to a storage unit by the measurement system and evaluated. Subsequently, the analysis apparatus supplies a user with sample-specific measurement values by way of an output medium, e.g., a monitor, a printer or a network connection.
Sample liquids or reagent liquids are usually transferred by means of automated pipetting devices. Such pipetting devices generally comprise a height-adjustable pipetting needle which is arranged vertically on a displaceable or pivotable transfer arm and which is connected to a pump unit such that a desired volume of a liquid can be taken from a container by way of the pipetting needle and discharged into a target container at a different location. Usually, the pipetting needle is displaced to a position over a liquid container with the aid of the transfer arm and then lowered into the liquid container and into the liquid contained therein. Once the desired volume has been removed, the pipetting needle is driven upward and then driven to the desired target position over a liquid container, for example, over a measurement cell, with the aid of the transfer arm. There, the pipetting needle is lowered again, and the quantity of liquid is discharged.
It is conventional to equip pipetting devices with a fill-level sensor. The purpose of this is, firstly, to be able to determine the fill level of reagent liquids in reagent liquid containers during the operation of the automated analysis apparatus and report this to the control unit. This ensures, for example, that a user can be informed in good time about the necessary replacement of a reagent container. Secondly, determination of the fill level ensures that the pipetting needle is always immersed sufficiently deeply into the liquid to be removed, in order to avoid air being sucked in instead of liquid.
The most common method for determining the fill level is the determination of the fill level by capacitive means. To this end, the pipetting needle consists of an electrically conductive material and thus in principle forms the measurement electrode, and it furthermore comprises a reference electrode. The fill level can be determined continuously from the change in the electric capacitance between the pipetting needle and the reference electrode. Another method entails determining the fill level by optical means. To this end, the pipetting needle comprises an optoelectronic fill-level sensor consisting of a light source and a light sensor. In the case of immersion, the light is refracted by the liquid and it no longer reaches the light sensor, or it only reaches the latter in attenuated form. The fill level can be determined from the attenuation of the light signal.
A problem is that foam can form on the liquid surface in individual liquid containers. Liquid foam, i.e., air bubbles surrounded by liquid, often arises in surfactant-containing reagent liquids or also if, when pipetting a liquid volume, it is not only liquid but also air that is taken up and is discharged into a target container. The presence of foam on the liquid surface makes it difficult to determine the fill level of the liquid, since the foam is already detected as liquid upon immersion of a pipetting needle equipped with a fill-level sensor. This usually has the effect of detecting a false fill level that is too high, which in turn has the consequence that, upon removal of liquid, at least part of the volume that is sucked in consists of foam. This leads to pipetting inaccuracies, which ultimately lead to incorrect measurement results.
Various approaches for the avoidance of pipetting inaccuracies as a consequence of foam formation are known in the prior art.
EP-A1-0526210 describes a method in which, by means of a pipetting needle equipped with a fill-level sensor, the fill level in a reagent liquid container is determined before and after the suctioning of a liquid volume. If the change in the fill level in relation to a previously fixed value is abnormal, this indicates the presence of foam.
EP-A1-0990907 describes another method in which, by means of a pipetting needle equipped with a fill-level sensor, a continuous determination of the fill level is carried out during the immersion of the needle, and a logic unit is used to determine whether foam is present and, if yes, measures are introduced such that the liquid surface is detected under the foam.
A disadvantage is that, in order to avoid pipetting inaccuracies, liquid containers in which foam was detected trigger an alarm or a warning in the automated analysis apparatus or are automatically excluded from further removal of liquid. This has the effect that analyses cannot be carried out and that, in some cases, a user needs to replace the liquid container.
A further problem is that, by movement of liquid containers, liquid residues can adhere to the inner wall of the container above the liquid surface, resulting in a container with a fill level that is initially too low.